CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling.
Proc Natl Acad Sci U S A
; 119(3)2022 01 18.
Article
em En
| MEDLINE
| ID: mdl-35031565
ABSTRACT
CD169+ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTß) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTßR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTßR revealed that both receptors contribute equally to LN CD169+ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTßR and RANK with implications for the immune response.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Baço
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Transdução de Sinais
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Receptor beta de Linfotoxina
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Receptor Ativador de Fator Nuclear kappa-B
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Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico
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Linfonodos
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Macrófagos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article